Optical stimulators are widely used to generate patterns of light for illumination of the retina of a subject. For convenience, in this specification, the term “optical stimulator” will be used to embrace stimulators emitting either visible or non-visible light, or both. The subject's response to the stimulus may be conscious or not. For example, the responses can be:                (i) from the neural retinal, as in the ERG (Electroretinogram) and its variants, PERG (Pattern ERG), focal ERG or mfERG (multifocal ERG), detected by one or more electrodes on or near the anterior surface of the eye,        (ii) from the optic nerve, as in the VEP (Visually Evoked Potential), detected by one or more electrodes at the back of the skull,        (iii) from the visual cortex or other brain areas as detected by electrodes in various locations on the skull as in an EEG (electroencephalogram)as perceived and reported by the subject, as in (micro)perimetry, or a large variety of psychophysics experiments or diagnostics which attempt to measure responses from various processing locations and levels in the visual system.        
For convenience, the term electroretinogram will be used herein to embrace systems in which any of responses (i), (ii), (iii) and (iv) are evoked by optical stimulation of the eye, specifically the retina, and detected using attached electrodes. However, some responses (iv) might be detected by other means, for example by the subject activating a pushbutton switch.
These responses are evoked using an optical stimulator to apply optical stimuli to the eye. It is known to use halogen lamps or other discrete light sources for simple stimuli, while cathode ray tubes (CRTs) have been preferred for generating more complex optical stimuli. Although CRTs have seen widespread use in optical stimulators, they are not entirely satisfactory for a variety of reasons. For example, the patterns are “painted” pixel by pixel, horizontal line by horizontal line, with a fixed frame rate, typically 60 or 75 frames per second. They generate an impulse of light from each pixel as the electron beam excites the phosphor and which lasts for a few milliseconds. The spectral content of the stimuli is determined by the phosphors used and, apart from limited adjustment of the red, green, blue [RGB] mix, cannot be altered or controlled by the user. In general, frame rates are those useful for displaying video (typically 100 Hz or less) and are fixed, i.e. all frames will have the same duration. Typical luminance levels for CRTs are between 100 and 400 candelas/sq. meter which might be adequate for some stimuli but perhaps too low for others. Moreover, the luminance levels decrease as the CRT ages. Finally, the commercial availability of CRTs has been declining and clinicians, experimenters and instrument makers have been actively seeking suitable alternatives.
Alternatives include liquid crystal display (LCD) and light emitting diode (LED) screens and arrays of large numbers of discrete LEDS. However, these alternatives also are not entirely suitable for use in optical stimulators. Like CRTs, they usually have a fixed frame rate but now the stimulus is on for most of the frame period, going from 1 to 2 milliseconds with a CRT to 13 milliseconds or 16 milliseconds (75 Hz and 60 Hz frame rates) with a LCD. This longer duration changes the assumptions on which many of the electrophysiology measurements are made, i.e. that the stimulus is an impulse. The pixel update proceeds by horizontal rows, with a change period of a few milliseconds as the liquid crystals rotate to a new position. During this time a moving band of light leakage from the backlight has been noted in many displays, which can degrade the optical stimulus spatial/temporal format. Attempts to ameliorate this problem included building custom controllers for the backlights to dim them during the pixel change period, leading to added complexity and expense.
Moreover, whereas CRTs were driven by analog signals, LCD displays usually are driven by digital signals. The resulting delay between the time that a frame is sent to the display and the time that frame is displayed can be a significant problem with LCDs because optical stimulators generally require exact timing between application of the stimulus and triggering of the response measurement. In fact, the standards for latency in some ERG measurements have had to be modified to deal with this effect and this issue has created difficulties in comparing results from the two systems and between measurements made using different LCD displays. Again, there is no user control of the wavelengths of the illumination; the LCD manufacturer picks the filters to apply to the white backlight to generate the display colors. An additional concern is that the light from LCD displays is polarized (as opposed to that of CRT based displays) and this may have some influence on the effect of the stimuli.
It is also known to project images directly on to the retina in the fields of information technology and entertainment where wearable displays have been developed. These displays generally use as the image source a compact LCD display and have the characteristic limitations of this technology as described above.
Many of the LCD problems also apply to the newer organic liquid crystal (OLED) displays with the exception of the light leakage problem which does not occur since the output of each pixel (LED) is directly controlled.
It has been proposed to use arrays of massed LEDs as optical stimulators. This allows spectral control (within practical limits of mounting hundreds of LEDS) and also allows for true impulse stimuli. A disadvantage of such LED arrays, however, is a lack of flexibility in the patterns produced since the LEDs are in fixed locations. In addition, the LEDS are seen as discrete light sources by the eye, which does not fit with most of the assumptions about the properties of optical stimulators.
A further limitation is that CRT and LCD displays and custom LED arrays are viewed at a distance by the patient and so the environmental and experimental conditions, ambient light, display luminance, distance etc., need to be controlled carefully because the illuminance of the stimuli on the retina depends on all these factors, plus the anterior clarity of the subject's eye and, last but not least, on the pupil diameter of the subject's eye.
In general, therefore, none of the above-described commercially available displays is entirely satisfactory for use optical stimulators:
It has been proposed to use, as another alternative, micro-mirror devices in optical stimulators. These have usually tried to take advantage of a commercially-available projector incorporating the micro-mirror device, typically known as a DLP (Digital Light Projector). A problem has been that these devices were designed to display video signals and use RGB lighting. This meant that there was a fixed frame rate, with the stimulus on for the full frame and no fine control over illumination. Also the commercial controllers made compromises with the detailed timing, which made their use as an optical stimulator very difficult. Typically, the incoming video stream is digitally adjusted to provide smooth video images and gamma values adjusted to replicate conventional displays.
DLP projectors have been investigated as optical stimulators, both in Maxwellian view and as viewed in front or back projection. Researchers report limitations caused by using conventional video drivers. For example, Packer et al. [Packer] disclosed a three DLP commercial projector but commented that they encountered limitations imposed by the video driver, specifically the limit on temporal performance imposed by the 63 Hz refresh rate.
Kuchenbecker et al. [Kuchenbecker] disclosed a single chip DLP projector modified to allow for nine LEDs, but which still used a VGA based video stream. Consequently, it too would be susceptible to the temporal limitations encountered by Packer et al.
Much the same applies to a DLP projector marketed as the PICO™ projector by Texas Instruments. It would not be entirely satisfactory for use in an optical stimulator because its frame timing and illumination periods did not have a regular output with an extra-long sub-frame occurring at the end of the nominal 60 Hz video input frame and for which the illumination was actually turned off.
Other limitations of known optical stimulators will be apparent from the following discussion of electroretinograms (ERG) and Visually Evoked Potential (VEP) systems for assessing functionality of the retinal and/or other parts of the visual system. As mentioned above, they employ optical excitation of a portion or portions of the retina and an electrical probe attached to the skin near the eye (in the case of ERG) or the rear of the head (in the case of VEP) or elsewhere to sense resulting electrical nerve impulses representing the processing and transport of information between the retina and the brain.
These impulses are generated by the rods and the cones and their associated nerve cells. These two sources have different spectral sensitivities and different dynamic responses, enabling their respective contributions to be distinguished. For cone assessment, a source near the photopic peak sensitivity wavelength of 555 nm is desirable. Moreover the dynamic response of cones is much faster, extending beyond 30 Hz.
One purpose of the ERG and VEP is to establish the retinal functionality at each location on the retina. The retinal cone density is non-uniform, being high in the central foveal region and lower in the peripheral regions. In order to obtain satisfactory signal levels in the peripheral regions, the spatial resolution demanded is reduced; the global objective is to create a cone map such that each retinal area to be sampled has approximately the same number of cones. A standard arrangement has each area being in the shape of a hexagon and all hexagons being sized according to cone density and clustered to fill all the available area leaving no gaps.
ERG/VEP visual stimuli may be classified as “pattern” or “multifocal”. The “pattern” type uses a systematic fixed pattern such as an alternating checkerboard or parallel bars. This measures the ganglion cell response. The multifocal type generates pseudo-random sequences both in terms of spatial and temporal arrangement and is capable of generating a spatial sensitivity profile or map across the retina. In various embodiments, an ERG system may use either type of stimulus and, for convenience, in this specification the term “pattern” may be used for both according to context, on the basis that each of the multiple points used in multifocal ERG/VEP constitutes a pattern. The custom focal ERG/VEP can address the response of a specified local retinal region. A typical stimulation arrangement uses an m sequence. The pattern stimulation arrangement uses cyclic summation, a technique of alternating stimulation where the frame cycle rate can be varied.
Where the ERG is captured using a single collection sensor, the location determination is made by directing light of known power to the required retinal location, where it should have a spatial dimension no larger than the required retinal resolution. An alternative to sequential scanning is the use of sequential multiplex projection, wherein various coded combinations of retinal areas are excited in sequence; during the subsequent processing, the contribution of each retinal area can be decoded. This technique is a form of multifocal ERG.
The multifocal method is analogous to the complement of pattern imaging where the target is uniformly illuminated but the image is captured using a single optical detector preceded by a temporal sequence of coded masks in a conjugate image plane. Multiplex methods generally result in a better image quality where the non-multiplexed limitation is the noise level of the sensor.
Previously known multifocal ERG art used coded images displayed on CRT's, or more recently LCD screens upon which the patient was required to stare for typically 10 minutes. In addition to the problem of patient movement, the displays do not generate as much light as is desirable for ERG purposes. Moreover, the amount of light captured by the eye is dependent on the pupil size, a quantity that varies with ambient light level and between people. Furthermore, the spectra of the three light channels (RGB) LCD screens and CRT monitors are satisfactory for visual displays but suboptimum for the purposes of ERG collection. In addition, the dynamic response of LCD displays, which may be fully adequate for consumer purposes, is a limiting factor for ERG investigations where greater speed can be useful. Finally, as mentioned above, the light from LCD displays is partially polarized rather than unpolarized that is preferable.
The capture process is very time consuming and makes it difficult or almost impossible to assure that the patient fixates consistently, a condition for avoiding uncertainty in the location on the retina.
As discussed above, the spectral content of the light emitted by the screens is controlled by the manufacturers of the screens and is, in many cases, non-ideal for stimuli for the retina and nerves and can vary from screen to screen. There are also issues in the way the frame is changed from one frame to the next. In a CRT the electron beam scans rows across the screen moving row by row from the top to the bottom. The phosphors are excited but then start to fade. There is also a flyback delay where the beam returns to the top. In a LCD screen the pixels do not change all at once either but are addressed sequentially in rows across the screen, creating a vertically moving band as the pixels change (quite slowly—over a few milliseconds) on the screen. These imperfections may be acceptable for video and computer monitor viewing but are not acceptable for some stimulus/response measurements. The subject also needs to be positioned in front of a screen and control of the ambient light levels and avoidance of distractions in the room is important. The luminance of screens is also an issue and in some cases can limit the experiments/assessments where more luminance would be desirable, i.e., to enable a faster flash or a brighter stimulus pattern.
A secondary area of interest has been in instrumentation capable of directly observing the stimulus on the retina. Various experiments have been tried using SLO (scanning laser opthalmoscopes) instruments to generate a stimulus and then observe its effect on the retina using laser imaging.